1 Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Japan.
2 Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
J Manag Care Spec Pharm. 2018 Nov;24(11):1146-1155. doi: 10.18553/jmcp.2018.24.11.1146.
Medication nonadherence is a major public health problem. Identification of patients who are likely to be and not be adherent can guide targeted interventions and improve the design of comparative-effectiveness studies.
To evaluate multiple measures of patient previous medication adherence in light of predicting future statin adherence in a large U.S. administrative claims database.
We identified a cohort of patients newly initiating statins and measured their previous adherence to other chronic preventive medications during a 365-day baseline period, using metrics such as proportion of days covered (PDC), lack of second fills, and number of dispensations. We measured adherence to statins during the year after initiation, defining high adherence as PDC ≥ 80%. We built logistic regression models from different combinations of baseline variables and previous adherence measures to predict high adherence in a random 50% sample and tested their discrimination using concordance statistics (c-statistics) in the other 50%. We also assessed the association between previous adherence and subsequent statin high adherence by fitting a modified Poisson model from all relevant covariates plus previous mean PDC categorized as < 25%, 25%-79%, and ≥ 80%.
Among 89,490 statin initiators identified, a prediction model including only demographic variables had a c-statistic of 0.578 (95% CI = 0.573-0.584). A model combining information on patient comorbidities, health care services utilization, and medication use resulted in a c-statistic of 0.665 (95% CI = 0.659-0.670). Models with each of the previous medication adherence measures as the only explanatory variable yielded c-statistics ranging between 0.533 (95% CI = 0.529-0.537) for lack of second fill and 0.666 (95% CI = 0.661-0.671) for maximum PDC. Adding mean PDC to the combined model yielded a c-statistic of 0.695 (95% CI = 0.690-0.700). Given a sensitivity of 75%, the predictor improved the specificity from 47.7% to 53.6%. Patients with previous mean PDC < 25% were half as likely to show high adherence to statins compared with those with previous mean PDC ≥ 80% (risk ratio = 0.49, 95% CI = 0.46-0.50).
Including measures of previous medication adherence yields better prediction of future statin adherence than usual baseline clinical measures that are typically used in claims-based studies.
This study was funded by the Patient-Centered Outcomes Research Institute (ME-1309-06274). Kumamaru, Kohsaka, and Miyata are affiliated with the Department of Healthcare Quality Assessment at the University of Tokyo, which is a social collaboration department supported by National Clinical Database. The department was formerly supported by endowments from Johnson & Johnson K.K., Nipro, Teijin Pharma, Kaketsuken K.K., St. Jude Medical Japan, Novartis Pharma K.K., Taiho Pharmaceutical, W. L. Gore & Associates, Olympus Corporation, and Chugai Pharmaceutical. Gagne has received grants from Novartis Pharmaceuticals and Eli Lilly and Company to the Brigham and Women's Hospital for unrelated work. He is a consultant to Aetion, a software company, and to Optum. Choudhry has received grants from the National Heart, Lung, and Blood Institute, PhRMA Foundation, Merck, Sanofi, AstraZeneca, CVS, and MediSafe. Schneeweiss is consultant to WHISCON and Aetion, a software manufacturer of which he also owns equity. He is principal investigator of investigator-initiated grants to the Brigham and Women's Hospital from Bayer, Genentech, and Boehringer Ingelheim unrelated to the topic of this study. He does not receive personal fees from biopharmaceutical companies. No potential conflict of interest was reported by the other authors.
药物依从性是一个主要的公共卫生问题。识别可能和不可能依从的患者可以指导有针对性的干预措施,并改善比较疗效研究的设计。
在大型美国行政索赔数据库中,评估多种患者先前药物依从性测量方法预测未来他汀类药物依从性的效果。
我们确定了一组新开始使用他汀类药物的患者,并在 365 天的基线期内使用比例天数覆盖(PDC)、缺乏第二剂和配药次数等指标衡量他们之前对其他慢性预防药物的依从性。我们在开始后一年测量他汀类药物的依从性,将 PDC 大于等于 80%定义为高依从性。我们从不同的基线变量组合和先前的依从性测量中构建逻辑回归模型,以随机抽取的 50%样本预测高依从性,并在另外 50%的样本中使用一致性统计量(c 统计量)测试其判别能力。我们还通过拟合所有相关协变量加先前平均 PDC 分类为<25%、25%-79%和≥80%的修正泊松模型,评估先前的依从性与随后的他汀类药物高依从性之间的关联。
在 89490 名开始使用他汀类药物的患者中,仅包含人口统计学变量的预测模型的 c 统计量为 0.578(95%CI=0.573-0.584)。结合患者合并症、医疗服务利用和药物使用信息的模型得出的 c 统计量为 0.665(95%CI=0.659-0.670)。使用每个先前药物依从性测量作为唯一解释变量的模型得出的 c 统计量范围在缺乏第二剂的 0.533(95%CI=0.529-0.537)到最大 PDC 的 0.666(95%CI=0.661-0.671)。在综合模型中加入平均 PDC 后,c 统计量为 0.695(95%CI=0.690-0.700)。在灵敏度为 75%的情况下,该预测因子将特异性从 47.7%提高到 53.6%。与平均 PDC 大于等于 80%的患者相比,之前平均 PDC 小于 25%的患者他汀类药物高依从性的可能性降低一半(风险比=0.49,95%CI=0.46-0.50)。
与基于索赔的研究中通常使用的常规基线临床测量相比,包含先前药物依从性测量的方法可以更好地预测未来的他汀类药物依从性。
这项研究由患者导向结果研究所(ME-1309-06274)资助。Kumamaru、Kohsaka 和 Miyata 隶属于东京大学医疗保健质量评估部,这是一个由日本国内临床数据库支持的社会合作部门。该部门曾得到 Johnson & Johnson K.K.、Nipro、Teijin Pharma、Kaketsuken K.K.、St. Jude Medical Japan、Novartis Pharma K.K.、Taiho Pharmaceutical、W. L. Gore & Associates、Olympus Corporation 和 Chugai Pharmaceutical 的捐赠支持。Gagne 收到了 Novartis Pharmaceuticals 和 Eli Lilly and Company 给布里格姆妇女医院的拨款,用于无关的工作。他是 Aetion 的顾问,这是一家软件公司,也是 Optum 的顾问。Choudhry 收到了美国国家心肺血液研究所、PhRMA 基金会、默克、赛诺菲、阿斯利康、CVS 和 MediSafe 的拨款。Schneeweiss 是 WHISCON 和 Aetion 的顾问,这是一家软件制造商,他也拥有该公司的股权。他是布里格姆妇女医院与本研究主题无关的拜耳、基因泰克和勃林格殷格翰公司的赠款的主要研究者。他不从生物制药公司收取个人费用。其他作者没有潜在的利益冲突。